Key information relevant to the recruitment process for the
overall study, such as dates of the recruitment period and locations

248 participants were randomized into the study in Cohort 1 (of which 244 were treated) and 240 participants were randomized into the study in Cohort 2 (of which 239 were treated).

Pre-Assignment Details

Significant events and approaches for the overall study
following participant enrollment, but prior to group assignment

4 participants in the trastuzumab subcutaneously then trastuzumab intravenously group and 1 participant in the trastuzumab intravenously then trastuzumab subcutaneously group did not receive any treatment and were not included in Participant Flow.

Reporting Groups

Description

Trastuzumab Subcutaneously Then Trastuzumab Intravenously

Participants received trastuzumab on Day 1 of each 3-week cycle for 8 cycles of the crossover period. During cycles 1-4, they received trastuzumab 600 mg subcutaneously (SC) and during cycles 5-8, they received trastuzumab 6 mg/kg intravenously (IV).

Trastuzumab Intravenously Then Trastuzumab Subcutaneously

Participants received trastuzumab on Day 1 of each 3-week cycle for 8 cycles of the crossover period. During cycles 1-4, they received trastuzumab 6 mg/kg intravenously (IV) and during cycles 5-8, they received trastuzumab 600 mg subcutaneously (SC). In case Cycle 1 of the cross-over period was the first cycle of trastuzumab treatment, a loading dose of trastuzumab 8 mg/kg IV was administered.

Cohort 1

Participants received trastuzumab 6 mg/kg intravenously on Day 1 of each 3-week cycle for up to 10 remaining cycles. Participants in Cohort 1, who had at least 2 treatment cycles remaining of their 18-cycle treatment course, were offered the opportunity to self-administer trastuzumab 600 mg subcutaneously using the single-injection device on Day 1 of each 3-week cycle under the direction of a trained health care practitioner. Following the end of treatment, participants were followed for 3 years for safety.

Cohort 2

Participants received trastuzumab 600 mg/kg subcutaneously on Day 1 of each 3-week cycle for up to 10 remaining cycles. Following the end of treatment, participants were followed for 3 years for safety.

Participant Flow for 4 periods

Period 1: Crossover Treatment 1

Trastuzumab Subcutaneously Then Trastuzumab Intravenously

Trastuzumab Intravenously Then Trastuzumab Subcutaneously

Cohort 1

Cohort 2

STARTED

243

240

0 [1]

0 [1]

COMPLETED

243

240

0

0

NOT COMPLETED

0

0

0

0

[1]

There were no participants in this reporting group in this period.

Period 2: Crossover Treatment 2

Trastuzumab Subcutaneously Then Trastuzumab Intravenously

Trastuzumab Intravenously Then Trastuzumab Subcutaneously

Cohort 1

Cohort 2

STARTED

241 [1]

237 [1]

0 [2]

0 [2]

COMPLETED

241

237

0

0

NOT COMPLETED

0

0

0

0

[1]

Not all participants who completed crossover treatment 1 started crossover treatment 2.

[2]

There were no participants in this reporting group in this period.

Period 3: Continuation Period

Trastuzumab Subcutaneously Then Trastuzumab Intravenously

Trastuzumab Intravenously Then Trastuzumab Subcutaneously

Cohort 1

Cohort 2

STARTED

0 [1]

0 [1]

226 [2]

206 [2]

COMPLETED

0

0

226

119

NOT COMPLETED

0

0

0

87

[1]

There were no participants in this reporting group in this period.

[2]

Not all participants who completed crossover treatment 2 started the continuation period.

Period 4: Safety Follow-up Period

Trastuzumab Subcutaneously Then Trastuzumab Intravenously

Trastuzumab Intravenously Then Trastuzumab Subcutaneously

Cohort 1

Cohort 2

STARTED

0 [1]

0 [1]

248 [2]

153 [3]

COMPLETED

0

0

22

12

NOT COMPLETED

0

0

226

141

[1]

There were no participants in this reporting group in this period.

[2]

All 248 randomized participants in Cohort 1 started the safety follow-up period.

[3]

Some of the participants in Cohort 2 were still receiving treatment and did not start this period.

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

Safety population: All participants who received at least 1 dose of trastuzumab.

Reporting Groups

Description

Trastuzumab Subcutaneously and Intravenously

Participants received trastuzumab on Day 1 of each 3-week cycle for 18 cycles. They either received trastuzumab 600 mg subcutaneously (SC) for 4 cycles followed by trastuzumab 6 mg/kg intravenously (IV) for 4 cycles or trastuzumab 6 mg/kg intravenously (IV) for 4 cycles followed by trastuzumab 600 mg subcutaneously (SC) for 4 cycles. For up to 10 remaining cycles, participants received either trastuzumab 6 mg/kg IV or trastuzumab 600 mg SC using the single-use injection device (Cohort 1) or trastuzumab 600 mg SC (Cohort 2).

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts
the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release
and can embargo communications regarding trial results for a period that is less than or equal to 60 days.
The sponsor cannot require changes to the communication and cannot extend the embargo.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release
and can embargo communications regarding trial results for a period that is more than 60 days but less than
or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.

Restriction Description:
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.